Whole-exome sequencing analysis of amniotic fluid cells in 5 pregnant women with thalassemia: Case report

While thalassemia is a monogenic disease that is relatively common worldwide, there is no recognized radical cure for thalassemia in current medical practice. Prenatal diagnosis is the most important contribution to thalassemia prevention, but due to its technical limitations, rare thalassemia mutations cannot be detected; and the birth of thalassemic babies cannot be completely circumvented. Whole-exome sequencing can, however, compensate for this shortcoming. PATIENT CONCERNS: We report the results of whole exon sequencing of amniotic cells in 5 pregnant women with thalassemia. DIAGNOSIS: Prenatal diagnosis revealed that 4 of them were α thalassemia carriers and 1 of them was β thalassemia carrier. INTERVENTIONS AND OUTCOMES: We collected amniotic fluid of 5 pregnant women (age range: 25–27 years, Mean ± SD: 28 ± 1.8) with thalassemia. The gestational ages ranged between 16 and 19 weeks. The cells were separated from the amniotic fluid and passaged until a sufficient number of cells were obtained for exome sequencing. We therefore employed whole-exome sequencing of amniotic fluid cells from thalassemic carriers to validate prenatal diagnostic results and to identify novel mutation sites. We found that 4 of 5 samples are SEA which is consistent with the clinical prenatal diagnosis. However, 2 of 5 samples were point mutations in the HBB gene, and were thus different from the clinical prenatal diagnosis. CONCLUSION: The identifications from this study showed that prenatal diagnosis has limitations. Whole-exome sequencing can compensate for this shortcoming. And this study would add new insights into understanding of molecular mechanisms in thalassemia.